Airway epithelial-derived factor relaxes pulmonary vascular smooth muscle.
The factors controlling the pulmonary vascular resistance under physiological conditions are poorly understood. We have previously reported on an apparent cross talk between the airway and adjacent pulmonary arterial bed where a factor likely derived from the bronchial epithelial cells reduced the magnitude of agonist-stimulated force in the vascular smooth muscle. The main purpose of this investigation was to evaluate whether bronchial epithelial cells release a pulmonary arterial smooth muscle relaxant factor. Conditioned media from SPOC-1 or BEAS-2B, a rat- and a human-derived bronchial epithelial cell line, respectively, were utilized. This media significantly relaxed precontracted adult but not fetal pulmonary arterial muscle in an oxygen tension-dependent manner. This response was mediated via soluble guanylate cyclase, involving AKT/PI3-kinase and neuronal nitric oxide synthase. Airway epithelial cell-conditioned media increased AKT phosphorylation in pulmonary smooth muscle cells (SMC) and reduced intracellular calcium change following ATP stimulation to a significantly greater extent than observed for bronchial SMC. The present data strongly support the evidence for bronchial epithelial cells releasing a stable and soluble factor capable of inducing pulmonary arterial SMC relaxation. We speculate that under physiological conditions, the maintenance of a low pulmonary vascular resistance, postnatally, is in part modulated by the airway epithelium.
Farah
Omar R
OR
The Hospital for Sick Children, 555 Univ. Ave., Toronto, Ontario, Canada M5G 1X8.
Li
Dongge
D
McIntyre
Brendan A S
BA
Pan
Jingyi
J
Belik
Jaques
J
D000818:Animals; D001980:Bronchi / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D006162:Guanylate Cyclase / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology / Q000502:physiology*; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000502:physiology*; D000071756:Soluble Guanylyl Cyclase; D014661:Vasoconstriction / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology
D017077:Culture Media, Conditioned; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D002118:Calcium